Based on published observations that the ventilated lung was injured during ischemia, before reperfusion, and preliminary studies suggesting that both addition of glucose and reduction of intravascular volume worsened this injury, and that antioxidant enzyme (AOE) gene expression was induced during ischemia, this proposal will investigate the following hypotheses: (1) Injury during ventilated ischemia is caused by generation of oxygen radicals, which increase permeability by activating protein kinase C (PKC) (2) Glucose may worsen this injury by augmenting oxygen radical generation or PKC activation, (3) Decreasing intravascular volume may worsen injury by altering mechanical forces acting on the vessel walls, thereby decreasing production of nitric oxide (NO). Decreased NO could exacerbate injury, as NO can scavenge superoxide anion, or activate cGMP, thereby relaxing endothelial cells and enhancing barrier function, and (4) Increased expression of AOE during ischemia may be caused by oxygen radicals or the cytokines, tumor necrosis factor- alpha and interleukin-1 (IL-1).